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Biomedical subjects

D Perry

Publications and source records attributed to D Perry.

At least 19 recordsLinked to original sources
PubMed1998

Range spectra in electron penetration problems.

The theory of electron penetration as predicted by the Fokker-Planck equation is first reviewed within a restricted context that considers the multiple scattering and transport of charged particles. We then broaden the context and show that range straggling effects also fit successfully into this framework, which completes an electron model initiated by Yang. We introduce those effects with a superposition of Fokker-Planck solutions, i.e., by using an incident beam that contains a spectrum of initial energies, or equivalently, a set of csda ranges. Straggling effects appear to be a beam property in this approach but are returned to the material when we use it. All the information needed to construct the spectrum is obtained from a measurement of the electron rest charge distribution in polystyrene. To illustrate the correctness of this procedure, we consider the case of a 20 MeV electron beam incident on water. We predict the absorbed dose distribution as a function of depth and also measure it with an ionization chamber in a water tank. We find nearly perfect agreement between calculation and experiment in this case where all the results derive and apply to a clinically operational machine.

Electrons↗
PubMed1998

The effect of sire breed on the melting point and fatty acid composition of subcutaneous fat in steers.

Fatty acid composition and the melting point of subcutaneous fat was determined in 18 Hereford, 25 Brahman x Hereford, 22 Simmental x Hereford, and 15 Friesian x Hereford steers that were grown out on pasture at two sites and slaughtered when the mean weight of the Herefords at each site was ca. 450 kg. Multivariate and univariate analyses tested the relations of fatty acid composition, degree of saturation, and melting point with sire breed, environment, age, and carcass characteristics. Hereford and Brahman steers were fatter than the Simmental and Friesian steers. Fat from Brahman-sired steers had a melting point 2.5 degrees C lower than fat from the Bos taurus-sired steers at the same age and had a higher proportion of unsaturated fatty acids, independent of variation in carcass weight and fatness. Melting point and degree of saturation decreased as age increased. Step-down discriminant analyses identified a set of three acids (14:0, 16:0, and 17:1) that differed among sire breeds, independent of differences in melting point: the acids 14:0 and 16:0 discriminated between Brahman and Bos taurus steers and 17:1 between Hereford and Simmental and Friesian steers. Increase in fatness was associated with an increase in 17:1, but, at the same fatness, no acids discriminated among the Bos taurus-sired steers. The use of Bos indicus cattle or their crossbreeds in situations in which hard-setting fat is likely may mitigate the problem.

Adipose Tissue↗
PubMed1997

Bcl-2 antagonizes apoptotic cell death induced by two new ceramide analogues.

Ceramides which arise in part from the breakdown of sphingomyelin comprise a class of antiproliferative lipids and have been implicated in the regulation of programmed cell death better known as apoptosis. In the present study, two new synthetic ceramide analogues, N-thioacetylsphingosine and FS-5, were used in Molt 4 cells to induce cell death. Besides their cytotoxic effects at concentrations > or = 14 microM the data obtained clearly show that both analogues induced apoptosis at concentrations below this critical concentration as assessed by trypan blue exclusion and cleavage of the death substrate poly-(ADP-ribose) polymerase (PARP). Additional experiments in bcl-2-transfected Molt 4 cells revealed that the apoptotic but not the lytic effects of the analogues were antagonized by the apoptosis inhibitor Bcl-2. Furthermore, neither N-thio-acetylsphingosine nor FS-5 induced PARP cleavage in bcl-2-transfected Molt 4 cells indicating that the induction of apoptotic cell death by cell permeable ceramides is not due to unspecific disturbance of the cell membrane.

Amides↗
PubMed1997

Intolerance to protein hydrolysate infant formulas: an underrecognized cause of gastrointestinal symptoms in infants.

The purpose of this study was to determine the effectiveness of an amino acid-based infant formula in infants with continued symptoms suggestive of formula protein intolerance while they were receiving casein hydrolysate formula (CHF). Twenty-eight infants, 22 to 173 days of age, were enrolled; each had received CHF for an average of 40 days (10 to 173 days) and continued to have bloody stools, vomiting, diarrhea, irritability, or failure to gain weight, or a combination of these symptoms. Sigmoidoscopy with rectal biopsy was performed in all infants. The infants then received an amino acid-based infant formula, Neocate, for 2 weeks. After 2 weeks of treatment, 25 of the infants demonstrated resolution of their symptoms and underwent challenge with CHF. Of the 25 who were challenged, eight tolerated the CHF and the remainder had recurrence of their symptoms. The histologic features in these infants varied from eosinophilic infiltration to normal. We conclude that not all infants with apparent formula protein-induced colitis respond to CHF and that these infants may have resolution of their symptoms when fed an amino acid-based infant formula.

Dietary Proteins↗
PubMed1997

Analysis of swainsonine and its early metabolic precursors in cultures of Metarhizium anisopliae.

The alpha-mannosidase inhibitor swainsonine is produced by the filamentous fungus Metarhizium anisopliae. The primary metabolite pathway from which it is derived is known to be that leading to lysine. In order to effect improvements in the yield of swainsonine it is of interest to study the changes in the intracellular levels of lysine and its biosynthetic intermediates, as well as swainsonine itself, which accompany changes in culture conditions or in the genetics of the microbe. Czapek-Dox defined medium has been used for these studies. A reversed-phase, high performance liquid chromatography procedure was developed for the analysis of lysine, saccharopine, alpha-aminoadipic acid and pipecolic acid in mycelial extracts. The method is based upon precolumn derivatization with 9-fluorenylmethyl chloroformate (FMOC), a reagent known to be useful for the derivatization of amino-containing compounds. Elution with an acetate buffer/acetonitrile gradient effected separation of the four metabolites which were quantified by UV absorption at concentrations from 1 to 20 microg ml(-1). Swainsonine concentrations were determined using a previously described enzyme-based method, but applied now to intracellular as well as extracellular samples. Analysis of mycelial extracts from the end of swainsonine accumulation in medium supplemented with L-lysine revealed the accumulation of pipecolic acid and to a lesser extent lysine compared to control mycelium. Controlling the culture medium pH to 9.0 resulted in a drop in swainsonine yield accompanied by an increase in intracellular pipecolic acid levels. Spontaneous mutants tolerant to the presence of the toxic lysine analogue 2-aminoethylcysteine (AEC) were isolated in an attempt to generate lysine over-producers, which might be expected to produce more swainsonine. Surprisingly, four independently isolated mutants produced lower yields of swainsonine, but accumulated higher levels of saccharopine. The tolerance to AEC therefore appears to be due to a reduction in the diversion of saccharopine into swainsonine biosynthesis, allowing the biosynthesis of sufficient lysine to overcome AEC competition.

2-Aminoadipic Acid↗
PubMed1997

Gastroenteric inflammation in children with ulcerative colitis.

This is a retrospective review of five pediatric cases of inflammatory bowel disease with gastroduodenal as well as pancolonic inflammation. The presumptive diagnosis was Crohn's disease in all. Three of five also had microscopic ileitis. Chronic active gastritis was present at diagnosis in all five and duodenitis in four of five. None ever had noncaseating granulomas in any location. Prolonged (mean, 22 months) and ineffective trials of multiple medical therapies were carried out before subtotal proctocolectomy, which allowed the diagnosis of ulcerative colitis to be made in all children. Surgery remained curative after follow-up of over 1 yr (mean, 16 months). This experience confirms that gastroduodenal inflammation occurs in children with ulcerative colitis. Presence of gastroduodenal inflammation does not ensure the diagnosis of Crohn's unless other characteristic features of Crohn's are present. Accurate discrimination between Crohn's and ulcerative colitis remains important in management of pediatric inflammatory bowel disease to facilitate timely surgical referral. Upper gastrointestinal tract inflammation in ulcerative colitis warrants further study.

Adolescent↗
PubMed1996

(1S,2R)-D-erythro-2-(N-myristoylamino)-1-phenyl-1-propanol as an inhibitor of ceramidase.

In this study, we have examined the cellular and biochemical activities of the ceramide analog (1S,2R)-D-erythro-2-(N-myristoylamino)-1-phenyl-1-propanol (D-erythro-MAPP). Addition of 5 microM D-e-MAPP to HL-60 human promyelocytic leukemia cells resulted in a concentration- and time-dependent growth suppression accompanied by an arrest in the G0/G1 phase of the cell cycle; thus mimicking the action of exogenous ceramides. Its enantiomer L-e-MAPP was without effect. Two lines of evidence suggested that D-e-MAPP may not function as a direct analog of ceramide. First, D-e-MAPP possesses a stereochemical configuration opposite to that of D-erythro-ceramide. Second, D-e-MAPP failed to activate ceramide-activated protein phosphatase in vitro. Therefore, we examined if D-e-MAPP functioned indirectly by modulating endogenous ceramide levels. The addition of D-e-MAPP to cells, but not L-e-MAPP, caused a time- and concentration-dependent elevation in endogenous ceramide levels reaching greater than 3-fold over baseline following 24 h of treatment. Both D-e-MAPP and L-e-MAPP underwent similar uptake by HL-60 cells. D-e-MAPP was poorly metabolized, and remained intact in cells, whereas L-e-MAPP underwent a time- and concentration-dependent metabolism; primarily through N-deacylation. In vitro, L-e-MAPP was metabolized by alkaline ceremidase to an extent similar to that seen with C16-ceramide. D-e-MAPP was not metabolized. Instead, D-e-MAPP inhibited alkaline ceramidase activity in vitro with an IC50 of 1-5 microM. D-e-MAPP did not modulate the activity of other ceramide metabolizing enzymes in vitro or in cells, and it was a poor inhibitor of acid ceramidase (IC50>500 microM). Finally, D-e-MAPP inhibited the metabolism of L-e-MAPP in cells. These studies demonstrate that D-e-MAPP functions as an inhibitor of alkaline ceramidase in vitro and in cells resulting in elevation in endogenous levels of ceramide with the consequent biologic effects of growth suppression and cell cycle arrest. These studies point to an important role for ceramidases in the regulation of endogenous levels of ceramide.

Acid Ceramidase↗
PubMed1996

Group B Streptococcus and preterm premature rupture of membranes: a randomized, double-blind clinical trial of antepartum ampicillin.

OBJECTIVE: Our purpose was to determine whether ampicillin prolongs the latency period after preterm premature rupture of membranes in patients colonized with group B Streptococcus. STUDY DESIGN: Sixty patients presenting at < or = 35 weeks' gestation with preterm premature rupture of membranes were included in the study. Cervical, vaginal, and perianal cultures for group B premature rupture were obtained. The participants then were randomized to receive either ampicillin or placebo intravenously for 24 hours and then orally until hospital discharge or delivery. All patients were treated without the use of tocolytic drugs. The chi(2) test, Fisher exact test, Student t test, and Wilcoxon signed-rank test were used for statistical analysis when appropriate. RESULTS: Fifteen patients had cultures positive for group B Streptococcus. Patients with cultures positive for group B Streptococcus who received ampicillin (n = 8) were more likely not to have been delivered of their infants 48 hours after preterm premature rupture of membranes than patients who received placebo (n = 7), a statistically significant difference (100% vs 43%; p = 0.01; relative risk 2.3; 95% confidence interval 1.2 to 4.5). Seven days after preterm premature rupture of membranes, however, there was no significant difference in percentage of patients with cultures positive for group B Streptococcus who remained undelivered (63% vs 29%; p = 0.19; relative risk, 2.2; 95% confidence interval 0.7 to 7.1). Among patients with cultures negative for group B Streptococcus, there was a trend for patients who received ampicillin to remain undelivered 48 hours after preterm premature rupture of membranes compared with those who received placebo, but the difference was not statistically significant (87% vs 64%; p = 0.07; relative risk, 1.4; 95% confidence interval 1.0 to 1.9). There also was no difference in percentage of patients with cultures negative for group B Streptococcus who remained undelivered 7 days after preterm premature rupture of membranes 39% vs 27%; p = 0.40; relative risk, 1.4; 95% confidence interval 0.61 to 3.3). There were no differences between the treatment and placebo arms of the group B Streptococcus positive and negative cohorts in incidence of cesarean section, chorioamnionitis, postpartum endometritis, or neonatal infectious morbidity. CONCLUSION: Use of antibiotics increases the percentage of patients with cultures positive for group B Streptococcus who remain undelivered 48 hours after preterm premature rupture of membranes. Antibiotic therapy may provide a window of opportunity for maternal treatment with corticosteroids to decrease the risk for neonatal morbidity among these preterm gestations.

Adult↗
PubMed1995

ADP-ribosylation factor functions synergistically with a 50-kDa cytosolic factor in cell-free activation of human neutrophil phospholipase D.

Proteins in both the cytosol and plasma membrane are needed to reconstitute cell-free phospholipase D activity from phagocytes (Olson, S., Bowman, E. P., and Lambeth, J. D. (1991) J. Biol. Chem. 266, 17236-17242); membrane factors include a small GTP-binding protein in the Rho family (Bowman, E., Uhlinger, D. J., and Lambeth, J. D. (1993) J. Biol. Chem. 268, 21509-21512). ADP-ribosylation factor (ARF) was recently implicated as the cytosolic factor, as it activates phospholipase D in HL-60 membranes. Herein, we show that ion exchange chromatography separates ARF from the major phospholipase D-stimulating cytosolic factor. Both bovine brain ARF and recombinant human ARF-1 stimulated a small amount of phospholipase D activity in the absence of cytosol (about 10% of the response seen with cytosol). With a high concentration of ARF-depleted cytosol, ARF did not further activate. However, at low cytosol, ARF caused marked activation. Thus, ARF synergizes with the cytosolic factor in phospholipase D activation.

ADP-Ribosylation Factors↗
PubMed1995

A property level analysis of lexical semantic representation in Alzheimer's disease.

In order to assess the hypotheses that Alzheimer's disease (AD) results in a property level restructuring, loss, or degradation of lexical-semantic knowledge, Alzheimer's patients and normal elderly subjects were presented with a property verification task in which they were asked to judge the truth value of telegraphic statements which paired objects with their properties (e.g., "Apple is red."). Objects with either high- or low-typical exemplars of categories (e.g., "oak" is a high typical exemplar of the category "tree." while "palm" is a less typical item). Properties were varied with respect to normatively determined dominance (e.g, "fins" is a high dominant property of "trout," while "slimy" is a less dominant property) and whether they were distinctive (i.e., served to distinguish between subsets of exemplars within a category) or shared among most or all category members (e.g., "stem" for the category "fruit"). Analyses of accuracy and reaction time data suggested that AD results in neither a loss per se of representation of properties, nor a reorganization of relations between objects' properties. However, results were consistent with a property level degradation of AD patients' object concepts. While there was no evidence for a differential degradation of distinctive vs shared properties, results suggested that AD patients have degraded representations of lower dominant properties and properties of low-typical category exemplars.

Aged↗
PubMed1995

Sustained increase in haemoglobin and RBC following long-term administration of recombinant human erythropoietin to patients with homozygous beta-thalassaemia.

Recombinant human erythropoietin (rHuEPO) was given subcutaneously three times per week in an escalating dose from 500 u/kg to 950 u/kg together with ferrous fumarate 305 mg and folic acid 5 mg/d, to 10 patients from four unrelated Arab families with homozygous beta-thalassaemia. Six splenectomized patients showed a mean (+/- standard error) increase in haemoglobin from 7.1 +/- 0.1 to 9.3 +/- 0.1 g/dl (P = 0.0001), in RBC from 4.0 to 5.0 x 10(12)/l (P = 0.0001) and in nucleated RBC from 32 +/- 7 x 10(10)/l to 82 +/- 6 x 10(10)/l while receiving 750 u/kg three times per week which persisted for 4-11 months. In two patients there was no need for further blood transfusions. In three out of four unsplenectomized patients there were no changes in Hb and RBC despite dose escalation. There were no significant changes in MVC, MCH and reticulocyte count, serum bilirubin, LDH, malonyldialdehyde (MDA) and vitamin E levels. After 13 weeks of rHuEPO there was a mean increase in the percentage of F cells from 31 +/- 10% to 86 +/- 6% (P < 0.003) in three splenectomized patients and in one unsplenectomized patient from 56.4% to 80% without changes in the levels of Hb F. Globin chain synthesis ratios did not change in four responding patients. Mean serum iron and transferrin saturation index did not change, whereas mean serum ferritin increased from 299 +/- 45 micrograms/l to 480 +/- 20 micrograms/l (P < 0.001). In seven responding patients an accelerated linear growth was indicated by positive changes in height standard deviation score for chronological age. Side-effects were minimal throughout the treatment period.

Administration, Cutaneous↗
PubMed1995

Coronary artery bypass grafting in an achondroplastic dwarf.

To our knowledge, coronary bypass for complications of coronary artery disease in achondroplasia has not previously been described. Achondroplasia, in and of itself, is not a contraindication to coronary bypass. Although the anatomic reserve of saphenous vein is less in achondroplastic dwarfs than in people of normal stature, that vessel and the internal mammary artery can be harvested in routine fashion. A 60-year-old woman with several risk factors for coronary artery disease underwent successful bypass surgery, which included the use of both a saphenous vein and the left internal mammary artery.

Achondroplasia↗
PubMed1994

Postoperative intramyocardial abscess caused by mucormycosis.

We report the case of an intramyocardial abscess caused by mucormycosis that arose after cardiac operation. Several causes of immunosuppression in a 71-year-old woman were exacerbated after she underwent coronary revascularization. Before she died of multiple organ system dysfunction, a variety of supraventricular and ventricular arrhythmias, as well as complete heart block, developed, but the cause was not clear until autopsy revealed a large septal myocardial abscess due to mucormycosis.

Abscess↗